The distribution of sodium and potassium in sub-cellular compartments of muscle fibers will be investigated using radioactive tracer and analytical flame photometric methods. The uniformity of the sodium distribution in muscle fibers will be investigated by loading muscles with isotopic sodium for different periods of time and subsequently measuring the specific activity of tracer sodium that is lost to initially sodium-free Ringer solution. When muscles become depleted of potassium and enriched with sodium, it has been observed in this laboratory that K42 no longer serves as an accurate tracer of flux. It is believed that an outer depot of muscle potassium, under these conditions, exchanges more rapidly with external sodium than does the bulk intracellular potassium. This compartmentalization of potassium in muscle will be investigated by the general method described for sodium. Potassium efflux from muscle is reduced when either K or Na ions are removed from the external medium. The suggested K ion:K ion and K ion: Na ion ionic exchanges will be investigated in detail by studying potassium efflux as a function of the external potassium ion concentration using a variety of cations to replace sodium ions in the medium. In addition, Rb, Cs, Mg, Ca and Ba ions have been observed to inhibit potassium efflux. By studying potassium efflux as a function of the concentration of the inhibiting cation, the affinities of membrane sites regulating potassium movements in muscle for cations in this series can be determined. The objective is to characterize the membrane sites involved in the K ion:K ion and K ion:Na ion exchanges by their ion binding characteristics.